Vajo Z, Szekacs B, McDonald M H, Takahashi B, Srivathsan K, Dachman W D
Department of Medicine, Maricopa Medical Center, Phoenix, Arizona, USA.
J Cardiovasc Pharmacol. 1999 Aug;34(2):316-9. doi: 10.1097/00005344-199908000-00018.
Bradykinin is a nonapeptide, whose mechanism of vasodilation is mediated chiefly through the release of endothelium-derived relaxing factor (EDRF). Diminished vasodilatory response to EDRF has been demonstrated in many pathologic states such as hypertension, atherosclerosis, diabetes, and long-term, heavy smoking. We studied whether the diminished EDRF-mediated vasodilatory response seen in chronic diseases can be demonstrated in young, clinically healthy smokers. We used the dorsal hand-vein compliance technique, an in vivo technique used to measure response to local infusions of vasoactive substances. Full dose-response curves to bradykinin (dosing range, 0.5-500 ng/min) were generated in 11 young, healthy smokers and 11 young, healthy nonsmokers by using hand veins preconstricted with phenylephrine (dosing range, 20-6,800 ng/min). In addition, after a washout period, a single maximal dose of a non-endothelium-dependent vasodilator, isoproterenol (300 ng/min) was infused. Our results demonstrated that smokers had a greater maximal venodilation to bradykinin than did nonsmokers (106 +/- 40% vs. 69 +/- 49%; p < 0.05). The log of the dose that produced half-maximal response to bradykinin was smaller in smokers: -0.10 +/- 0.93 (0.79 ng/min) versus 0.75 +/- 0.84 (5.6 ng/min); p < 0.05. There was no difference in the maximal dilatory response to isoproterenol: 80 +/- 45% (smokers) versus 89 +/- 50% (nonsmokers), nor was there a difference in the log dose of phenylephrine necessary to produce 80% constriction of the hand vein (2.7 +/-0.7 vs. 2.7 +/- 0.9 ng/min) between the two groups. We conclude that young, otherwise healthy smokers have a paradoxic hyperactive response to the endothelium-dependent vasodilator, bradykinin, but maintain a similar response to the nonendothelium-dependent vasodilator, isoproterenol as compared with nonsmokers. Their reactivity to the alpha1-adrenergic agonist phenylephrine was found to be intact. It is possible that a hyperactive response to EDRF in young smokers contributes to endothelium damage seen in chronic disease. To our knowledge, this is the first report on increased reactivity to bradykinin in short-term smokers.
缓激肽是一种九肽，其血管舒张机制主要通过释放内皮源性舒张因子（EDRF）介导。在许多病理状态下，如高血压、动脉粥样硬化、糖尿病和长期大量吸烟，对EDRF的血管舒张反应减弱已得到证实。我们研究了在年轻的临床健康吸烟者中，是否能证实慢性疾病中出现的EDRF介导的血管舒张反应减弱。我们使用手背静脉顺应性技术，这是一种用于测量对局部注入血管活性物质反应的体内技术。通过使用用去氧肾上腺素（给药范围为20 - 6800 ng/min）预收缩的手静脉，在11名年轻健康吸烟者和11名年轻健康非吸烟者中生成了缓激肽（给药范围为0.5 - 500 ng/min）的完整剂量反应曲线。此外，在洗脱期后，注入单次最大剂量的非内皮依赖性血管舒张剂异丙肾上腺素（300 ng/min）。我们的结果表明，吸烟者对缓激肽的最大静脉舒张反应比非吸烟者更大（106±40%对69±49%；p<0.05）。吸烟者中产生对缓激肽半数最大反应的剂量对数更小：-0.10±0.93（0.79 ng/min）对0.75±0.84（5.6 ng/min）；p<0.05。对异丙肾上腺素的最大舒张反应没有差异：80±45%（吸烟者）对89±50%（非吸烟者），两组之间产生手静脉80%收缩所需的去氧肾上腺素对数剂量也没有差异（2.7±0.7对2.7±0.9 ng/min）。我们得出结论，年轻的、其他方面健康的吸烟者对内皮依赖性血管舒张剂缓激肽有反常的高反应性，但与非吸烟者相比，对非内皮依赖性血管舒张剂异丙肾上腺素保持相似的反应。发现他们对α1肾上腺素能激动剂去氧肾上腺素的反应性是完整的。年轻吸烟者对EDRF的高反应性可能导致在慢性疾病中看到的内皮损伤。据我们所知，这是关于短期吸烟者对缓激肽反应性增加的首次报告。
